Medications are essential to preventing and treating many illnesses. Americans receive an average of 12, and those aged 65 years and older receive more than 30 prescriptions each year. This degree of medication use creates the potential for drug-drug interactions (DDIs). Injury due to a known DDI is a preventable adverse drug event and serious medication error. Evidence suggests that hundreds of millions of interacting drugs are co-prescribed each year, ultimately exposing hundreds of millions of patients to these known hazards. Although the exact magnitude of harm associated with DDIs is not known, clinically significant interactions occur, resulting in potentially life-threatening consequences. Electronic prescribing and pharmacy information systems include DDI alerts as a form of clinical decision support (CDS) to warn prescribers and pharmacists of potentially harmful medication combinations, and provide them with necessary information to avoid or mitigate the risk of patient harm. Today, every pharmacy and soon every physician office and health care organization will employ some form of health information technology that will include DDI alerts. However, use of this technology to improve patient safety has not lived up to its promise. In particular, research has shown the current DDI alert system is broken. This application requests partial support for a solution-oriented conference series aimed at improving the implementation of meaningful DDI alerts within CDS. The long- term goals are to develop an ongoing structured process to improve the quality of DDI alerting systems used by health providers to maximize the value of this technology, and ultimately improve patient safety. At these conferences, experts, stakeholders, and public-private partnerships will develop strategies for explicit, systematic evaluation of DDIs to improve knowledge base data and the practical utility of electronic clinical decision aids. Specific aims of the conference series are to: 1) develop guidelines for systematic appraisal of DDI evidence; 2) recommend principles for including DDIs in drug safety alerts; and 3) establish preferred strategies for presenting DDI alerts. In summary, this application will address an important public health issue regarding improving health information technology as a healthcare safety net, and will, ultimately lead to improved medication use and patient safety throughout the nation.